Original Investigation

Human Genetics

, Volume 111, Issue 1, pp 75-87

Sequence polymorphism at the human apolipoprotein AII gene (APOA2): unexpected deficit of variation in an African-American sample

  • Stephanie M. FullertonAffiliated withDepartment of Anthropology, Pennsylvania State University, 409 Carpenter Building, University Park, PA 16802, USA
  • , Andrew G. ClarkAffiliated withInstitute of Molecular Evolutionary Genetics, Department of Biology, Pennsylvania State University, University Park, PA 16802, USA
  • , Kenneth M. WeissAffiliated withDepartment of Anthropology, Pennsylvania State University, 409 Carpenter Building, University Park, PA 16802, USA
  • , Scott L. TaylorAffiliated withDepartment of Molecular Biotechnology, University of Washington, Seattle, WA 98195-7730, USA
  • , Jari H. StengårdAffiliated withDepartment of Epidemiology and Health Promotion, KTL-National Public Health Institute, Helsinki, Finland
  • , Veikko SalomaaAffiliated withDepartment of Epidemiology and Health Promotion, KTL-National Public Health Institute, Helsinki, Finland
  • , Eric BoerwinkleAffiliated withHuman Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77225-0334, USA
  • , Deborah A. NickersonAffiliated withDepartment of Molecular Biotechnology, University of Washington, Seattle, WA 98195-7730, USA

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Abstract.

A 3.3-kb region, encompassing the APOA2 gene and 2 kb of 5' and 3' flanking DNA, was re-sequenced in a "core" sample of 24 individuals, sampled without regard to the health from each of three populations: African-Americans from Jackson (Miss., USA), Europeans from North Karelia (Finland), and non-Hispanic European-Americans from Rochester, (Minn., USA). Fifteen variable sites were identified (14 SNPs and one multi-allelic microsatellite, all silent), and these sites segregated as 18 sequence haplotypes (or nine, if SNPs only are considered). The haplotype distribution in the core African-American sample was unusual, with a deficit of particular haplotypes compared with those found in the other two samples, and a significantly (P<0.05) low level of nucleotide diversity relative to patterns of polymorphism and divergence at other human loci. Six of the 14 SNPs, whose variation captured the haplotype structure of the core data, were then genotyped by oligonucleotide ligation assay in an additional 2183 individuals from the same three populations (n=843, n=452, and n=888, respectively). All six sites varied in each of the larger "epidemiological" samples, and together, they defined 19 SNP haplotypes, seven with relative frequencies greater than 1% in the total sample; all of these common haplotypes had been identified earlier in the core re-sequencing survey. Here also, the African-American sample showed significantly lower SNP heterozygosity and haplotype diversity than the other two samples. The deficit of polymorphism is consistent with a population-specific non-neutral increase in the relative frequency of several haplotypes in Jackson.